March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Neuroprotective Role of Sirtuin (SIRT1) Against Hypoxia in Retinal Ganglion Cells
Author Affiliations & Notes
  • Don K. Davis, Jr.
    Ophthalmology, Univ of Florida HSC-Jacksonville, Jacksonville, Florida
  • Sankarathi Balaiya
    Ophthalmology, Univ of Florida College of Med, Jacksonville, Florida
  • K V Chalam
    Ophthalmology, Univ of Florida-Jacksonville, Jacksonville, Florida
  • Sandeep Grover
    Ophthalmology, University of Florida College of Medicine, Jacksonville, Florida
  • Footnotes
    Commercial Relationships  Don K. Davis, Jr., None; Sankarathi Balaiya, None; K V Chalam, None; Sandeep Grover, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1958. doi:
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      Don K. Davis, Jr., Sankarathi Balaiya, K V Chalam, Sandeep Grover; Neuroprotective Role of Sirtuin (SIRT1) Against Hypoxia in Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1958.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Retinal ganglion cells (RGC) are vital for conveying information from the neuroretina. Hypoxia induced apoptosis is responsible for reducing RGC viability in chronic ocular disorders. Sirtuin 1 (SIRT1) is important for preserving cell viability during hypoxia. We will investigate SIRT1’s role in sustaining RGC viability during hypoxia.

Methods: : Differentiated RGCs (RGC-5) using staurosphorine received varying hypoxic concentrations (100-500 µM) of cobalt chloride (CoCl2) for 24hrs. Hypoxia induced cell viability was assessed by WST-1 assay. SIRT1’s role in promoting viability was determined indirectly via sirtinol (SIRT1 inhibitor). Hypoxia induced apoptosis was evaluated by measuring stress activated protein kinase/c-JUN N-terminal kinase (SAPK/JNK) and caspase 3 activity.

Results: : CoCl2 concentrations greater than 200 µM resulted in significantly reduced RGC viability (p = 0.01). SIRT1 levels increased significantly (p < 0.01) during CoCl2 treatment: 100 (6.5-fold), 200 (6-fold), 300 (3.5-fold), and 400 µM (4.5-fold). Phosphorylated SAPK/JNK increased 36-fold (200 µM CoCl2 concentration), then plateaued at the 300 (25-fold) and 400 (27.8-fold) µM CoCl2 concentrations (p < 0.01). Caspase 3 activity increased with CoCl2 and sirtinol (p < 0.05) treatment. Sirtinol reduced RGC viability and SIRT1 levels (p < 0.01) while having higher effect on SAPK/JNK phosphorylation.

Conclusions: : SIRT1 significantly influences RGC viability. Sirtinol’s effect reflects the interaction SIRT1 has with apoptotic signaling proteins. This investigation demonstrated SIRT1 importance in forestalling the effects of hypoxia induced apoptosis.

Keywords: ganglion cells • hypoxia 
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